An ability to quickly identify and quantify one or more analytes in a solution is desirable in many areas, including medical diagnostics, petroleum exploration, environmental health monitoring, and drug testing. Unfortunately, many conventional analysis systems and methods are time-intensive and can be quite complicated. In addition, many conventional analytical approaches require the use of consumable reagents or test strips, which require calibration for each use, are subject to degradation over time, often provide only a qualitative result, and can require coding.
Infrared spectroscopy represents an optical chemical analysis method that overcomes many of these drawbacks. Infrared spectroscopy interrogates a sample using an optical signal having a relatively broad wavelength range. Infrared light (electromagnetic radiation having a wavelength within the range of approximately 740 nanometers to approximately 300 microns) is typically transmitted through the sample such that each chemical constituent in the sample imparts spectral information on the outgoing optical signal. This spectral information manifests as intensity peaks at specific wavelength locations in a spectral plot of the output signal, wherein the positions, magnitudes, and inflections of these peaks (i.e., the “spectral fingerprint”) are indicative of the constituent chemicals in the sample.
Initially developed for use in outer space exploration, spectral fingerprinting based on spectroscopy (infrared- and/or visible-light spectroscopy) has been used to measure Doppler shifts caused by radial velocity changes of distant suns in the search for exo-planets potentially orbiting around them. In order to effectively measure such small effects, however, a spectrometer requires careful calibration and an absolute wavelength reference. In space applications, iodine is often used for these purposes. Iodine is an attractive reference because a temperature-controlled iodine vapor cell is spectrally rich over a useful wavelength range. Specifically, iodine has sixty-seven precise and non-variant spectral features over the wavelength range from 389.5 nanometers (nm) to 681.5 nm. An iodine vapor cell is added to the optical path of the interferometer so that the light from the distant sun can pass through it. The spectral features in the light from the sun are then verniered against the iodine spectral features. The Doppler shift of the sun's spectra, therefore, can be precisely determined relative to the absolute locations of the spectral features of the iodine.
The medical industry has embraced infrared spectroscopy for some analytical applications, such as blood analysis, blood flow kinetics, brain scanning, and the like. Unfortunately, infrared spectroscopy, as conventionally practiced, has several drawbacks.
First, the typical analytes of interest normally exist at extremely low concentrations (parts-per-million or even lower concentrations) in a body fluid or blood, the bulk of which (approximately 80%) is water. Typically, the spectral characteristics of the water swamp the relatively small spectral contributions of the targeted analytes, which makes it extremely difficult to identify and/or quantify the analytes.
Second, although much of the analyte-specific spectral information is located in the mid-infrared wavelength range (i.e., 2.5 microns to 12.5 microns), water has a high absorption coefficient in this wavelength range. As a result, prior-art infrared spectroscopy systems have focused on the near infrared wavelength range (i.e., infrared wavelengths<2.5 microns) to mitigate signal attenuation due to water absorption.
Third, interference from protein and water absorption spectra typically precludes univariant calibration that would enable quantification of analytes present in a bodily fluid. Further, in many such applications, the use a separate calibration chemical in the analysis of a chemical mixture is highly undesirable. Still further, in many cases, the addition of more spectral information by using a calibration chemical would often serve only to further confound the analysis of the sample.
A common approach to mitigate some of these issues and enable some quantification of the analytes is to collect the blood (or other bodily fluid) so that it can be held in a container of known thickness during analysis. This enables the estimation of the concentration of the analyte that is based on the known path length of the infrared light through the sample. The need to draw blood increases patient discomfort and anxiety, however. It also represents a potential health risk to the caregiver. Ideally, blood analysis would be performed non-invasively by transmitting the infrared radiation through a thin-tissue region of the body, such as the ear lobe or webbing between the fingers. Unfortunately, it is extremely difficult to quantify the measured analytes in the blood in such systems due to the fact that the precise path length of the light through the tissue is indeterminate.
Infrared spectroscopy fluid analysis has applicability to many applications outside of medicine as well, such as remote sensing, industrial process control, environmental monitoring, pollution control, and criminology. Some such applications require an ability to monitor analytes in background solvents other than water. In addition, many require a sensor system suitable for operation in extremely harsh conditions. For example, distributed sensors can be used to more effectively control chemical or drug synthesis systems, thereby increasing product quality, lowering costs, and reducing generation of undesirable chemical byproducts. Further, remote sensors having improved sensitivity and accuracy can improve geological exploration, detection of enemy activity, and detection of treaty violations using, for example, unmanned vehicles such as drones. Of course, water-based non-medical applications exist as well, such the accurate detection and quantification of analytes in groundwater or industrial plant effluent, which would enable better detection of drinking water contamination, faster detection of industrial plant effluent pollution, or detection of impurities due to fracking operations, thereby improving public safety, improving environmentally friendly energy generation, and protecting the environment.
An ability to quantify one or more analytes in a background solution high accuracy and throughput would represent a significant advance of the state-of-the-art.